Compositions and Methods for Hair Regrowth

ABSTRACT

The invention provides compositions and methods for promoting hair growth and reducing hair loss using bioactive extracts of curcumin, Withania somnifera, and saw palmetto. Tocotrienols, tocopherols, piperine extract, low molecular weight collagen, and hyaluronic acid are optionally included in the compositions and methods.

Throughout this application various publications are referenced. Thedisclosures of these publications in their entireties are herebyincorporated by reference into this application in order to more fullydescribe the state of the art to which this invention pertains.

FIELD OF THE INVENTION

The present invention relates to the field of hair loss, and moreparticularly to the restoration of hair growth.

BACKGROUND OF THE INVENTION

Hair loss (alopecia) is a widespread problem affecting about 80 millionmen and women in the United States alone according to the AmericanAcademy of Dermatology. The $7 billion hair loss industry is a testamentto the significance and the scope of the issue. The most commonalopecias are androgenic alopecia, telogen effluvium and alopeciaareata.

Androgenic alopecia (AGA) is the most common type of hair loss in bothsexes, affecting at least 50% of men by the age of 50 and up to 40% ofwomen in mid-adult life. More recently AGA is being referred to as malepattern hair loss (MPHL) and female pattern hair loss (FPHL) to reflectthe differences in clinical presentation and the new science on thepathophysiology of the conditions, which support the modernunderstanding that hair loss is due to the contribution of otherfactors, besides androgens and genetic disposition, particularly inFPHL.

In humans, individual hair follicles progress through phases of growthindependent of one another. They are subject to and respond individuallyto the influence of several inductive and inhibitory signaling moleculesin the follicle environment. Anagen, the growth phase, generally lastsbetween 2 to 7 years in a healthy follicle. Catagen is a transitionalphase of regression that lasts approximately 2-3 weeks between thegrowth phase and the resting phase. Telogen, the resting phase, lastsfor approximately 3 months. The late stage of telogen is associated withthe regeneration of the next growth phase. Loss of coverage, or hairthinning and hair loss, occurs when the normal cycling and growth ofnumerous follicles are disrupted. The disruption can be widespread,sudden and synchronized causing immediately visible loss or it can beslow, steady and unsynchronized, becoming visible over a long period oftime, only when 50% of the follicles have been affected. Hair densityand volume decreases when the hair growth cycle is disrupted and morefollicles enter catagen and telogen prematurely, while not enoughfollicles enter anagen to replace them. Further, miniaturization, thesignature pathology seen in patients with MPHL & FPHL, can occur wherethe width of hair fibers progressively decrease in each consecutivecycle causing once thick and long hair fibers to become thinner,lighter, barely visible vellus-like hairs.

A modern view on alopecia describes all hair loss, regardless of itsvarious manifestations and traditional classifications, as the result ofa ‘disordered hair follicle.’ (Breitkopf, T., Dermatol. Clin., 2013,31(1):1-19). When hair follicles on the scalp are in an unbalanceddisordered state, it compromises their function and manifests in hairgrowth and cycle abnormalities. Different combinations of abnormalitiespertain to different disorders. The traditional view held by researchersand clinicians considers hair loss as a disease, which has led toalopecias being classified by their presumed respective causes and/ormanifestations. For instance, MPHL/FPHL and telogen effluvium (TE) areclassified as non-inflammatory, whereas alopecia areata (AA) andscarring alopecias are classified as inflammatory diseases. Recentfindings have begun to challenge this perspective as researchers havefound that even in MPHL/FPHL there is significant evidence ofmicro-inflammation, a term proposed to reflect the indolent inflammatoryprocess in AGA. (Mahe, Y. F., Int. J. Dermatol., 2000, 38(8):576-84).Thus, it is being recognized that in all alopecias there are multiplecombinations of factors, like inflammation, that underlie the disorderedhair follicle.

The hair growth cycle is primarily maintained through the complexinterplay of numerous cytokines, growth factors and transcriptionfactors that signal the cells of the follicles to either induce orprohibit hair growth. These signals are both introduced extrinsicallyand also produced intrinsically by the follicle's dermal papilla cells(DPCs) that determine follicle and hair fiber characteristics Thoseextrinsic controls that induce early catagen and inhibit growth, such asthe androgen dihydroxytestosterone (DHT), have provided targets fortherapies, such as the drug finasteride in the case of DHT. However,even extrinsic factors act on the follicles by altering the productionof signaling molecules by the follicle DPCs. The significance of immunesignaling and balance in sustaining proper follicle functioning isfurther underscored by the fact that it represents one of the few sitesof ‘immune privilege’ (IP) in the body. The follicle's IP normallyprotects the follicle from immune system recognition and inflammatoryattack. IP also works to sequester anagen-associated autoantigens withinthe follicle, protecting them from immune recognition. Studies haveshown that the follicle's IP can be compromised by stress-inducedneuropeptides such as Substance P (SP) (Peters, E. M., Am. J. Pathol.,2007, 171(6):1872-86) and cytokines such as interferon gamma (IFN-γ).(Xing, L., Nat. Med., 2014, 20(9):1043-49). Subsequent to this immunesystem imbalance and collapsed IP, compromised follicles are subject toinflammatory attack. Thus for a follicle to not become ‘disordered’ andto produce healthy hair, it is vital to maintain an IP.

Inflammatory responses can be further stimulated by the presence of freeradicals, also referred to as Reactive Oxygen Species (ROS). ROS arehighly reactive molecules with unpaired electrons that can directlydamage cellular structures and alter DNA. They are generatedendogenously through normal and specific metabolic processes and we aresubject to ROS exposure from the environment, for instance in the formof common air pollutants. However, with age, the body's ability toneutralize ROS decreases since production of antioxidant enzymes andendogenous antioxidants decreases with age while ROS generationincreases with age resulting in increased oxidative stress on the body,including hair. Compromised hair follicles are known to be particularlyvulnerable to ROS from environmental stressors. Further, inflammatoryresponses, through positive feedback, create a cyclic cascade andgenerate even more ROS. For example, it has been shown in androgeninduced alopecia that the generation of ROS mediates thepro-inflammatory androgen signaling cascade. Similarly, in models ofchronic stress, the neurogenic inflammatory pathways of SP were shown toincrease ROS and decrease innate antioxidant defenses, leading to hairgrowth arrest and hair cycle arrest.

Thus, the common underlying pathway of hair loss can be seen asdisordered immune signaling and an oxidative imbalance that involvenumerous players: pro-inflammatory cytokines, pro-fibrotic and growthinhibiting factors like TGF-β, and inflammatory cells—all perpetuatedthrough chronic generation of free radicals, oxidative stress andfurther inflammatory changes and immune imbalances. This common pathwayin hair loss can be triggered and propagated by several factorsincluding, but not limited to: sudden changes or severe imbalances innutrition as in crash diets, androgens, genetics, and stress.

Androgens, like other steroid hormones, act on target cells by diffusingthrough the plasma membrane, binding to specific receptors and thenacting on the DNA, inducing the transcription and translation ofspecific hormone-regulated genes and their products, such as cytokines.In the follicle, testosterone is mostly metabolized by 5α-reductase(5-ar) into DHT. DHT is implicated in the pathogenesis of severalandrogen responsive disorders such as prostate disease, acne and AGA. Itis now recognized that the effects of androgens within follicles aremediated via signaling cascades, which are dysregulated in pathologieslike hair loss. The main action of DHT on follicles occurs within thedermal papilla cells, where it binds to androgen receptors, enters thenucleus and leads to increased transcription and overproduction ofgrowth-inhibiting molecules like the cytokine TGF-β that signals catageninduction and apoptosis. Once triggered by minimal amounts of DHT, otherfactors can maintain the pathophysiology of AGA without the presence ofandrogens, as seen in men with MPHL who were castrated after puberty.Thus, it appears that blocking androgens alone to combat hair loss isinsufficient due to the presence of signaling and dysregulation of theimmune balance downstream of the initial insult, triggering a cascade ofnumerous immune and inflammatory processes that can sustain the alopecicpathway. In fact, androgen-induced overproduction of TGF-β by the DPC'sand surrounding fibroblasts also plays a role in perifollicular fibrosisand inflammation—implicated in the pathophysiology of miniaturization infollicles. Of special note, MPHL and FPHL differ in that women have lesstotal 5-ar than men. This may account for why current drug therapiesthat block 5-ar to treat alopecia produce minimal results in women ascompared to men, especially given that systemic DHT and 5-ar aregenerally within normal limits in women with FPHL.

Stress has long been disputed as playing a measurable role in hair loss.Recent research, however, has begun to examine the roles ofpsycho-emotional stress, nerves and immune cells in hair growth and hasdiscovered new pathways that link the central nervous system with thehair follicle. New evidence provides definable neurological,neuroendocrine and immunological mechanisms through which stress caninhibit hair growth. Psycho-emotional stress results in systemicelevation of nerve growth factor, a key modulator of hair growthtermination, and substance P (SP), the prototypic stress-associatedneuropeptide that is widely acknowledged as a potent modulator of immuneresponses and neurogenic inflammation of the skin. In addition tocompromising follicle IP, elevated levels of SP induce the proliferationand degranulation of local mast cells and these mast cells in turnrelease a host of pro-inflammatory mediators like histamine andcytokines like TNF-α. The resulting neurogenic inflammation has beenshown to cause hair growth arrest and promotion of follicle regression.The follicle has also been shown to be highly sensitive to stresshormones like cortisol, which are known to cause catagen induction, andthe follicle even contains all the needed machinery to self-producethese hormones. Specifically, one of the major stress hormones,corticotropin-releasing hormone (CRH), is elevated systemically duringstress and can bind to the follicle, which induces the follicle toproduce even more CRH and cortisol.

There are limited options regarding pharmaceutical therapeutics for thetreatment of AGA in the United States, and only one is indicated forFPHL. One therapeutic, is minoxidil. While minoxidil's mechanism ofaction has not been clarified despite its use since 1988 in thetreatment of AGA, it is widely believed to elongate the anagen phase byacting on potassium channels in the hair follicle, thereby improvingfollicular circulation. Some known side effects of minoxidil aredizziness, chest pain, difficulty breathing and swelling. The topicalversion has the further side effects of causing rashes and skinirritations in some users. The other FDA-approved therapeutic,finasteride, is only indicated in MPHL. It works by competitivelybinding the enzyme 5-ar, thereby reducing the conversion of testosteroneinto DHT, which is a known androgen trigger for hair loss. Finasterideis FDA-approved for treatment of AGA only in men and has also beenreported to cause side effects of erectile dysfunction, ejaculatorydysfunction and loss of libido in a segment of users.

The complexity of the hair loss pathway requires a multi-prongedapproach to treat the most prominent aspects of the problem.Pharmaceutical therapies such as minoxidil and finasteride achieve somesuccess in treating hair loss, but ultimately only address singleelements of a larger problem, not addressing downstream dysregulatedsignaling or the common pathway of inflammation and oxidative stress.Additionally, they are associated with potential significant anddebilitating side effects. There is a need for a therapy which inaddition to addressing just one trigger, like androgens, also addressesthe disordered immune signaling of catagen-inducing cytokines andaddresses the inflammation that is both a result and a promoter of thedisordered signaling. An ideal therapeutic should further address thegeneration and effect of ROS in hair loss due to the role of oxidativestress in aggravating inflammation. And, importantly, there is a needfor a therapy which can also address psycho-emotional stress and itseffects on hair loss. Finally, there is a need for a therapy that issafe and does not induce similar side effects.

Nutraceutical formulations and the multi-targeting bioactive propertiesof certain plant phytonutrients offer a possible solution since they cantarget multiple triggers of hair loss at once. Further, the fact thatthese phytonutrients are natural in origin and known to be safe forconsumption avoids many of the concerns of undesired side effects, whichare common with pharmaceuticals.

One such phytonutrient is curcumin (diferuloyl methane) which is foundin the rhizome of the turmeric plant, Curcuma longa, and is readilyextracted from the plant, U.S. Pat. No. 5,861,415. Curcumin has beenshown to slow hair loss by down-regulating expression of the DHT-bindingAndrogen Receptor, inhibit type II 5-ar, support regrowth by decreasinglevels of the catagen-signaling cytokine TGF-β and to be a potentantioxidant and anti-inflammatory agent. (Pumthong, G., J. Dermatolog.Treat., 2012, 23(5):385-92). It has significant activity againstpro-inflammatory cytokines like TNF-α and IL-1, both known to signalcatagen and to inhibit follicle growth. Curcumin's anti-stress andneuroprotective properties have been studied extensively and oneneurotransmitter it inhibits is Substance P, which in high levels hasbeen shown to compromise the follicle's immune privilege and to inducemast cell degranulation that leads to catagen, hair growth inhibitionand increased inflammation. As for its safety profile, curcumin has notbeen shown to evidence toxicity in human studies at doses of up to 8000mg daily for three months. (Cheng, A. L., Anticancer. Res., 2001,21(4B):2895-2900).

Another phytonutrient is Withania somnifera, commonly known asAshwagandha. It is a medicinal plant that has been employed forcenturies in ayurvedic medicine and has recently been observed to reducehair loss. (Kalani, A., BMJ Case Rep., 2012). Ashwagandha has also beenrecognized as an adaptogen, a unique class of herbal ingredients thatresult in the restoration of normal physiological function(homeostasis), and to increase the body's resistance to the effects ofstress, such as by decreasing cellular sensitivity to stress.Ashwagandha is known to rebalance and lower the levels of the stresshormone cortisol, to improve thyroid function, and to elevate the body'sendogenous antioxidant enzymes through its principal withanolides.Ashwagandha also exhibits inhibitory effects on pro-inflammatorycytokines such as IL-6 and TNF-α. The active compounds in Withaniasomnifera leaves and roots are C28 steroidal lactone molecules known aswithanolides, such as Withaferin A, and are extracted from the plantusing known methods, U.S. Pat. No. 7,108,870.

Extracts of Serenoa repens or “saw palmetto,” a dwarf palm tree, havebeen observed to help hair regrowth in male pattern baldness. (Chittur,S., Evid. Based Complement Alternat. Med., 2011:985345). The sawpalmetto berry contains over 100 known compounds. The active ingredientsin saw palmetto are contained in the purified lipid soluble extract ofthe saw palmetto berry. This has been found to contain 85 to 95 percentfatty acids (predominantly lauric, caprylic, and caproic), long chainalcohols, and sterols (including beta-sitosterol, stigmasterol,cycloartenol, lupeol, lupenone, and methylcycloartenol). Saw palmettonaturally inhibits the activity of the testosterone catalyzing 5-arenzyme, but unlike the drug finasteride it does not interfere withProstate Specific Antigen levels. In comparative studies withfinasteride, saw palmetto was even associated with an improvement ofsexual dysfunction. (Suter, A., Phytother. Res., 2013, 27(2):218-26).The berries also contain high molecular weight polysaccharides (sugars),which may reduce inflammation or strengthen the immune system.

Tocotrienols, together with tocopherols, which are members of theVitamin E family, possess potent antioxidant activity by directlyneutralizing reactive oxygen species and also raising the body's ownantioxidants and antioxidant enzymes. Tocotrienols have also been shownto provide protection against UV light and oxidative stress and topromote hair regrowth in humans. (Beoy, L. A., Trop. Life Sci. Res.,2010, 21(2):91-99). A natural source rich in tocotrienols andtocopherols is palm oil, with crude palm oil (also referred to as the“tocotrienol-rich fraction”) containing up to 800 mg/kg weight of α- andγ-tocotrienol isotypes. The distribution of vitamin E in palm oil is 30%tocopherols and 70% tocotrienols. Natural sources of vitamin E, such aspalm oil, are believed to have greater bioactivity than syntheticallymanufactured vitamin E.

Piperine, the active principle of the dried, unripe fruits of variousblack pepper plants, is an alkaloid which has been shown in in vitrostudies to protect against oxidative damage by inhibiting or quenchingfree radicals and reactive oxygen species. It has also been shown toenhance the bioavailability of a number of therapeutic drugs andphytonutrients like curcumin by strongly inhibiting hepatic andintestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase.(Srinivasan, K., Crit. Rev. Food Sci. Nutri., 2007, 47(8):735-48). Inaddition to possessing antioxidant properties, piperine has further beenshown to possess analgesic and anti-inflammatory properties in animalstudies. (Tasleem, F., Asian Pac. J. Trop. Med., 2014, 7S1:S461-8).

It is an object of the present invention to provide a nutraceuticalsupplement composition that simultaneously inhibits the moleculartriggers of hair loss associated with stress and androgens and furtheraddresses the concurrent cascade of disordered cytokine signaling,inflammation and oxidative damage that is brought on by their activity,thereby preventing damage and shrinkage to hair follicles and promotingmore follicles to enter a healthy hair cycle in a multi-targeted,comprehensive manner.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides a composition for promotinghair growth and reducing hair loss, comprising from 100 to 1000 mg of anextract of Curcuma longa, from 100 mg to 1000 mg of an extract of theroots and leaves of Withania somnifera, and at least 200 mg of sawpalmetto extract. Advantageously, the composition further comprises from100 mg to 1000 mg of tocotrienols and tocopherols. The composition mayfurther comprise low molecular weight collagen and hyaluronic acid andthe collagen may be Type I and Type III collagen and have a molecularweight of less than 5000 daltons. The collagen may be present in anamount from 500 mg to 2000 mg, and said hyaluronic acid may be presentin an amount from 100 mg to 1000 mg.

The composition of the invention may further include at least 200 mg ofcurcumin, at least 100 mg of withanolides, at least 200 mg of sawpalmetto extract, and at least 100 mg of tocotrienols and tocopherolscomprising a complex of 78% tocotrienols and 22% tocopherols, at least1000 mg of Type I and III collagen having a molecular weight of lessthan 3000 Daltons, and at least 100 mg of hyaluronic acid.

The composition of the invention may further include at least 5 mg ofpiperine.

The composition of the invention may further include one or morecompounds from the group consisting of green tea extract, L-methionine,L-cysteine hydrochloride, resveratrol, capsaicin, biotin, selenium,Vitamin D, Vitamin A, and Vitamin C.

The invention provides a food item comprising the composition of theinvention, and a mixture of additional components selected from thegroup consisting of vitamins, amino acids, minerals, proteins,carbohydrates, fats, flours, flavoring, and sweetener.

The invention also provides a method of promoting hair growth andreducing hair loss by administering to a subject an effective amount ofthe composition of the invention, in a pharmaceutically suitablevehicle, for a time sufficient to promote hair regrowth and reduce hairloss in subjects exhibiting symptoms of alopecia.

Additional features, advantages, and aspects of the present disclosureare set forth or apparent from consideration of the following detaileddescription, drawings, and claims. Moreover, it is to be understood thatboth the foregoing summary of the present disclosure and the followingdetailed description are exemplary and intended to provide furtherexplanation without limiting the scope of the present disclosure asclaimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of the present disclosure, are incorporated in andconstitute a part of this specification, illustrate aspects of thepresent disclosure and, together with the detailed description, serve toexplain the principles of the present disclosure. In the drawings:

FIG. 1 depicts the androgen pathway and indicates where components ofthe invention help mitigate damage to hair follicles.

FIG. 2 depicts how the stress pathway may lead to hair loss andindicates where components of the invention help mitigate damage to hairfollicles.

FIG. 3 is a table depicting the subject's results of variousimplementations of the invention over a 7-month period.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides novel nutraceutical compositions whichhave been shown to reduce hair loss and promote the growth of new hairin individuals suffering from various types and degrees of hair loss.Current treatments for hair loss and promotion of hair growth fall undertwo categories: a) pharmacological or b) nutrient supplements.Pharmacological treatments come with the risk of significant sideeffects and nutrient supplements only provide nutrition while ignoringthe ongoing causes of the actual hair loss itself. A non-pharmacologicalnutraceutical formulation such as the current invention provides a muchneeded option for those who suffer hair loss, since it both addressesthe underlying causes of hair loss using natural remedies withoutpharmacological side effects and provides the nutrition needed forimproved hair growth. It can further be used as both a preventative andas a complementary therapy to augment pharmacological treatments.

The present invention provides compositions and methods for promotinghair health and hair growth. Without being bound by any particulartheory or explanation, the novel nutraceutical compositions of theinvention contain components which may synergistically inhibit multipletriggers of hair loss such as DHT (See FIG. 1) and the stress hormonecortisol (See FIG. 2); reduce inflammation and oxidative stressassociated with the self-sustaining common pathway of hair loss; andprovide necessary nutrition which may be better absorbed and utilized byhair follicles after the follicles are rebalanced by the othercomponents of the compositions of the invention.

In one implementation of the invention for promoting hair growth andreducing hair loss, the composition comprises curcumin, ashwagandha, andsaw palmetto.

In a preferred embodiment for male subjects, the composition includes atleast 200 mg of curcumin, at least 100 mg of withanolides, and at least500 mg of bioactive saw palmetto, preferably standardized to contain atleast 85% fatty acids and sterols.

In another preferred embodiment for hair regrowth and to reduce hairloss in female subjects, the composition of the invention furtherincludes at least 200 mg of bioactive saw palmetto extract, preferablystandardized to contain at least 85% fatty acids and sterols. Thisembodiment containing less saw palmetto is preferred in women due to thefact that women typically have 5 times less total testosterone than men.The same benefits can be achieved with less of this DHT inhibitor sincewomen have less testosterone which can be metabolized into DHT.

In a more preferred embodiment of the aforementioned compositions, thecompositions can additionally contain one or more of an effective amountof an extract from saw palmetto, tocotrienols, tocopherols, piperine,low molecular weight collagen, and hyaluronic acid.

The said saw palmetto extract is preferably a bioactive extract of theSerenoa repens plant. Methods for obtaining the bioactive components ofthe invention are known, for example, by extraction of plant materials,as described in U.S. Pat. No. 6,039,950. The components can further beobtained with increased bioactivity and/or bioavailability, using knownmethods for improving the bioavailability of bioactive componentsextracted from plants, resulting in the need for less of the bioactivecomponent as described in U.S. Pat. Nos. 8,329,233, 6,153,198, and5,891,465). The bioactive saw palmetto extract is further preferablystandardized to contain at least 85% fatty acids and sterols.

The tocotrienols and tocopherols for use in the compositions of theinvention may be combined in a complex containing 78% tocotrienols and22% tocopherols by weight.

The said low molecular weight collagen is preferably hydrolyzed Type Iand Type III collagen having a molecular weight of less than 3000daltons.

Thus, an implementation of a composition of the invention may include atleast 200 mg of curcumin, at least 100 mg of withanolides, at least 500mg of bioactive saw palmetto, preferably standardized to contain atleast 85% fatty acids and sterols, and one or more of the following: atleast 200 mg of saw palmetto extract, 10 mg to 1000 mg of tocotrienoland 50 mg to 1000 mg of tocopherols present in a complex comprised of78% tocotrienols and 22% tocopherols, at least 5 mg of piperine, 500 mgto 2000 mg of hydrolyzed Types I and III collagen having a molecularweight of less than 3000 daltons, and/or 100 mg to 1000 mg of hyaluronicacid.

For female subjects an implementation of a composition of the inventionmay contain at least 200 mg of curcumin, at least 100 mg ofwithanolides, and at least 200 mg of bioactive saw palmetto, preferablystandardized to contain at least 85% fatty acids and sterols, and one ormore of the following: at least 200 mg of saw palmetto extract, 10 mg to1000 mg of tocotrienol and 50 mg to 1000 mg of tocopherols present in acomplex comprised of 78% tocotrienols and 22% tocopherols, at least 5 mgof piperine, 500 mg to 2000 mg of hydrolyzed Types I and III collagenhaving a molecular weight of less than 3000 daltons, and/or 100 mg to1000 mg of hyaluronic acid.

The compositions of the invention may also include one or more of thefollowing ingredients: green tea extract, L-methionine, L-cysteinehydrochloride, resveratrol, capsaicin, biotin, selenium, Vitamin D,Vitamin A, and/or Vitamin C.

The invention further provides a method of promoting hair growth andreducing hair loss in a subject experiencing hair loss of the scalp, byadministering to the subject an effective amount (e.g. an amounteffective to promote hair regrowth, slow the progression of hair loss,etc.) of said composition comprising at least 200 mg of curcumin, atleast 100 mg of withanolides, and at least 200 mg of bioactive sawpalmetto, preferably standardized to contain at least 85% fatty acidsand sterols, and one or more of the following: at least 200 mg of sawpalmetto extract, 10 mg to 1000 mg of tocotrienol and 50 mg to 1000 mgof tocopherols present in a complex comprised of 78% tocotrienols and22% tocopherols, at least 5 mg of piperine, 500 mg to 2000 mg ofhydrolyzed Types I and III collagen having a molecular weight of lessthan 3000 daltons, and/or 100 mg to 1000 mg of hyaluronic acid.

The compositions and method of the invention for alleviating hair loss,may be effective to improve hair loss caused by, for example, forms ofalopecia including androgenetic alopecia, alopecia areata, alopeciamucinosa, telogen effluvium, chronic inflammation, extreme and/orchronic stress, diabetes, cellulitis, hair treatments, hereditarydisorders, hormonal changes, hyperthyroidism, hypothyroidism,malnutrition, lupus, medication side effects, including fromchemotherapy and birth control, radiation, aging and trichotillomania.

In an implementation, the invention provides methods for the treatmentand/or reduction of hair loss in a subject, comprising administering tothe subject in a pharmaceutically suitable vehicle, an effective amountof a composition of the invention comprising at least 200 mg ofcurcumin, at least 100 mg of withanolides, and at least 200 mg ofbioactive saw palmetto, preferably standardized to contain at least 85%fatty acids and sterols, and one or more of the following: at least 200mg of saw palmetto extract, 10 mg to 1000 mg of tocotrienol and 50 mg to1000 mg of tocopherols present in a complex comprised of 78%tocotrienols and 22% tocopherols, at least 5 mg of piperine, 500 mg to2000 mg of hydrolyzed Types I and III collagen having a molecular weightof less than 3000 daltons, and/or 100 mg to 1000 mg of hyaluronic acid.The compositions can additionally include further amounts of nutrientsnecessary and beneficial hair growth which are known to those havingordinary skills in the art.

“Pharmaceutically suitable vehicle” as used herein refers to a non-toxicsolid, semisolid (also referred to as “softgel”) or liquid filler,diluent, encapsulating material or formulation auxiliary of any type,suitable for the particular route of administration and desired releaserate (e.g. immediate or controlled release) of the active compounds, andare well known in the art. Pharmaceutically suitable vehicles andexcipients that may be used to formulate oral dosage forms are describedin the Handbook of Pharmaceutical Excipients, American PharmaceuticalAssociation, Arthur H. Kibbe (2000), incorporated herein by reference inits entirety.

The bioactive compounds in the compositions of the invention may becombined in a single dosage form or for unit-dose or multi-doseadministration. The compositions can be formulated into suitablepreparations for administration to a subject, such as solutions,suspensions, tablets, dispersible tablets, capsules, powders, sustainedrelease, for oral administration or in sterile solutions or suspensionsfor parenteral administration, as well as transdermal patch preparation,nasal formulation and dry powder inhalers et al. The compositions mayalso be formulated as liquid dosage forms such as elixir, suspension orsyrup. The compositions are formulated into compositions usingtechniques and procedures well known in the art.

Dosage of the therapeutic agent(s) of the invention is dependent uponmany factors including, but not limited to, the severity of the hairloss, the subject's age, general health and individual response to thecompositions of the invention. Accordingly, dosages of the compositionscan vary and be readily adjusted, depending on each subject's response.

In one implementation of the invention, the compositions of theinvention may be administered to a subject in an amount of at leastapproximately 1800 mg per day as a single dose, or may be divided intotwo or more dosages administered throughout a 24 hour period. Ingestingat mealtimes may improve absorption of some of the components of thecompositions of the invention. The time of day the given dose orfraction of the given dose is administered can vary by day. Thecompositions of the invention may be taken on a daily basis untildesired hair growth is achieved, or indefinitely.

In addition to oral dosage forms, the compositions of the invention maybe incorporated with other ingredients into food, for example by addingthe compositions to mixtures used to prepare a “food bar,” cookie, cakeor other edible item. Mixtures of ingredients for preparing nutritionbars and other baked and non-baked items are known. Flavoring andsweetener may be added to mask any “medicine taste” of the compositionsof the invention. Preservatives may be added to improve shelf life.

In accordance with the practice of the invention, the subject may be ahuman. The subject may also be a mammal, such as a monkey, ape, dog,cat, cow, pig, horse, sheep, rabbit, mouse, rat or a bird.

The person of ordinary skill in the art will recognize that additionalingredients can be used in the compositions and methods of the presentinvention, for example to promote hair health and appearance, whilemaintaining effectiveness or enhancing the activity of the compositionsin promoting hair growth and reducing hair loss.

Example 1

The male subject was a 49-year old male. He began to notice mild hairthinning at the age of 28. However, the hair loss became significantlymore pronounced after he underwent radiation therapy for thyroid cancerat the age of 32. Over the next 17 years, he went to numerous physiciansand took the only FDA-approved pharmaceuticals for hair loss (minoxidiland finasteride) but the improvement was minimal and didn't stall hisprogression to Stage III Vertex/Stage IV MPHL on the Hamilton-Norwoodscale. During this time he also tried several natural supplements andtopical formulations, but did not see any noticeable improvement. Priorto taking the implementations of the invention described herein, he hadtaken Serenoa repens alone and biotin alone, which did not result in anoticeable cessation of hair loss or new hair growth. In 2012 he wasadditionally diagnosed with Rheumatoid Arthritis (RA), which is anautoimmune condition that creates a pro-inflammatory state in the bodyand significantly affects joints. The subject was also suffering fromchronic stress at this time. The subject notes that as a result of hiscondition his hair loss and the quality of his hair also worsened.

The subject was first given Curcumin extracted from Curcuma Longastandardized to 95% Curcuminoids including: curcumin, desmethoxycurcumin, bis-desmethoxy curcumin and volatile oils of turmeric rhizome(BCM-95®, Dolcas-Biotech, LLC, Chester, N.J.) in amounts of at least 200mg a day. To improve curcumin absorption and bioavailability, it wastaken together with 5 mg of standardized extraction of piperine. Aftercontinuing this regimen for 3 months and in addition to improvement ofhis RA symptoms, he noted decreased hair shedding and slightly improvedhair thickness and quality. During month 4, the subject was additionallygiven a daily 250 mg dose of Ashwagandha extracted from Withaniasomnifera, containing at least 8% withanolide glycosides and 32%oligosaccharides from the roots and leaves (Sensoril®, Natreon, NewBrunswick, N.J.) for stress associated with his condition and work. Henoted that month that there was a further decrease in his hair loss andsome small growth of new hairs. During month 5, the subject wasadditionally given a daily dose of Certified Organic saw palmettoextract Standardized 85-95% fatty acids (Valensa Eustis, Fla.) in theamount of 640 mg a day. During that month he experienced significant newgrowth at the frontal hairline and temples, a decrease in hair loss andimprovement in hair quality. During month 6, the subject added a 100 mgdose of tocotrienol/tocopherol complex comprising 78% tocotrienols and22% tocopherols (Tocomax™ 20%, Carotech, Malaysia) a day. This additionlead to further improvement in new hair growth at the hairline and thevertex and his hair became less brittle and smoother. Lastly, in month7, He was additionally given approximately 1000 mg of hydrolyzed marinecollagen Types I and III (Youtheory, Tustin, Calif.) and 100 mg ofhyaluronic acid (NOW Foods, Bloomingdale, Ill.). At the end of month 7the subject reported improvement in hair density, thickness, andcontinued new hair growth. The subject's progression is tabulated inFIG. 3.

Before initiation of the experiment, the subject had a bald spot on hiscrown covering an area of approximately 78 cm². Upon evaluation after 7months, the results showed that the progression of his hair loss and therecession of the frontal hairline were stalled. There was also notableand measurable new growth at the hairline, temples and vertex. Theoriginal bald spot had been reduced to an area of approximately 38 cm²,or an increase of hair growth of approximately 40 cm². Further, therewas increase in the thickness and overall quality of hair.

After having significant loss of scalp hair for a period of 17 years,the subject experienced significant new hair growth and overall increasein thickness of scalp hair. The subject experienced no noticeable sideeffects from consumption of the composition.

Example 2

The subject, a 36 year-old male with early stages of MPHL (stage II onthe Hamilton—Norwood scale), began taking an implementation of theinvention consisting of 200 mg curcumin, 5 mg of piperine, 250 mg ofwithanolides, 640 mg of Serenoa repens, 100 mg Tocotrienol/Tocopherolcomplex comprising 78% tocotrienols and 22% tocopherols, 900 mg ofHydrolyzed Collagen Types I and III, 100 mg Hyaluronic Acid, 5 mgVitamin A, 3 mg Vitamin D, 60 mg Vitamin C, 0.2 mg Selenium, 3 mgBiotin, 5 mg Capsaicin, 50 mg Resveratrol, 100 mg L-Methionine and 100mg L-Cysteine Hydrochloride. After 6 months of daily ingestion thecomposition, he not only noticed a halt to the progression of hisalopecia, but he also noted new hair growth, especially in thefront—filling in his receding hairline. His hair also became thicker andmore manageable. His wife and colleagues noted the increased hair growthand thickness. He even decided to start growing his hair longer.Overall, he also noted that he was feeling overall much healthier andeven experienced increased libido.

Example 3

The subject was a 51 year-old female with moderate to severe stage 2(Ludwig scale) manifesting in typical female pattern hairloss—significant widening of the part, diffuse hair loss and thinning ofthe crown. She started noticing hair thinning and loss in her 20's andtried many different products, without improvement. She concurrentlysuffered from chronic stress. The subject began taking began taking animplementation of the invention consisting of 200 mg curcumin, 5 mg ofpiperine, 250 mg of withanolides, 200 mg of Serenoa repens, 100 mgTocotrienol/Tocopherol complex comprising 78% tocotrienols and 22%tocopherols, 900 mg of Hydrolyzed Collagen Types I and III, 100 mgHyaluronic Acid, 5 mg Vitamin A, 3 mg Vitamin D, 60 mg Vitamin C, 0.2 mgSelenium, 3 mg Biotin, 5 mg Capsaicin, 50 mg Resveratrol, 100 mgL-Methionine and 100 mg L-Cysteine Hydrochloride daily. After a 6 monthperiod, she saw dramatic improvement not only in quality and shine, butalso saw significant hair growth within 7 months of use.

Advantages of the Invention

The compositions of the invention thus produced significant and visiblebenefits in mitigating hair loss and promoted new hair growth.

While the present disclosure has been described in terms of exemplaryaspects, those skilled in the art will recognize that the presentdisclosure can be practiced with modifications in the spirit and scopeof the appended claims. These examples and embodiments given above aremerely illustrative and are not meant to be an exhaustive list of allpossible designs, aspects, applications or modifications of the presentdisclosure.

What is claimed is:
 1. A method of improving hair loss caused byandrogenetic alopecia, alopecia areata, alopecia mucinosa, telogeneffluvium, chronic inflammation, extreme and/or chronic stress,diabetes, cellulitis, hair treatments, hereditary disorders, hormonalchanges, hyperthyroidism, hypothyroidism, malnutrition, lupus,medication side effects, radiation, aging and trichotillomania,comprising administering to a subject in need thereof an effectiveamount of a composition comprising: 100 mg to 1000 mg of an extract ofCurcuma longa, from 100 mg to 1000 mg of an extract of the roots andleaves of Withania somnifera, at least 200 mg of saw palmetto extract,and a pharmaceutically acceptable encapsulating material, for a timesufficient to improve hair loss.
 2. The method of claim 1, wherein thecomposition further comprises from 100 mg to 1000 mg of tocotrienols andtocopherols.
 3. The method of claim 1, wherein the composition furthercomprises low molecular weight collagen and hyaluronic acid.
 4. Themethod of claim 3, wherein said collagen is Type I and Type III collagenand has a molecular weight of less than 5000 daltons.
 5. The method ofclaim 3, wherein said collagen is present in an amount from 500 mg to2000 mg, and said hyaluronic acid is present in an amount from 100 mg to1000 mg.
 6. The method of claim 1, comprising at least 200 mg ofcurcumin, at least 100 mg of withanolides, at least 200 mg of sawpalmetto extract, and further comprising at least 100 mg of tocotrienolsand tocopherols comprising a complex of 78% tocotrienols and 22%tocopherols, at least 1000 mg of Type I and III collagen having amolecular weight of less than 3000 Daltons, and at least 100 mg ofhyaluronic acid.
 7. The method of claim 1, wherein the compositionfurther comprises at least 5 mg of piperine.
 8. The method of claim 1,wherein the composition further comprises one or more compounds selectedfrom the group consisting of green tea extract, L-methionine, L-cysteinehydrochloride, resveratrol, capsaicin, biotin, selenium, Vitamin D,Vitamin A, and Vitamin C.
 9. A method of improving hair loss caused bymedication side effects, comprising administering to a subject in needthereof an effective amount of a composition comprising: 100 mg to 1000mg of an extract of Curcuma longa, from 100 mg to 1000 mg of an extractof the roots and leaves of Withania somnifera, at least 200 mg of sawpalmetto extract, and a pharmaceutically acceptable encapsulatingmaterial, for a time sufficient to improve hair loss.
 10. The method ofclaim 9, wherein the medication side effects are caused by chemotherapy.11. The method of claim 9, wherein the composition further comprisesfrom 100 mg to 1000 mg of tocotrienols and tocopherols.
 12. The methodof claim 9, wherein the composition further comprises low molecularweight collagen and hyaluronic acid.
 13. The method of claim 12, whereinsaid collagen is Type I and Type III collagen and has a molecular weightof less than 5000 daltons.
 14. The method of claim 12, wherein saidcollagen is present in an amount from 500 mg to 2000 mg, and saidhyaluronic acid is present in an amount from 100 mg to 1000 mg.
 15. Themethod of claim 9, comprising at least 200 mg of curcumin, at least 100mg of withanolides, at least 200 mg of saw palmetto extract, and furthercomprising at least 100 mg of tocotrienols and tocopherols comprising acomplex of 78% tocotrienols and 22% tocopherols, at least 1000 mg ofType I and III collagen having a molecular weight of less than 3000Daltons, and at least 100 mg of hyaluronic acid.
 16. The method of claim9, wherein the composition further comprises at least 5 mg of piperine.17. The method of claim 9, wherein the composition further comprises oneor more compounds selected from the group consisting of green teaextract, L-methionine, L-cysteine hydrochloride, resveratrol, capsaicin,biotin, selenium, Vitamin D, Vitamin A, and Vitamin C.